Selectivity Comparison of Tumor-Imaging Probes Designed Based on Various Tumor-Targeting Strategies: A Proof of Concept Study

Fluorescence probes are emerging as appealing tools for tumor imaging, although the discovery of ideal probes with high tumor selectivity and desirable tumor-to-normal contrast remains challenging. There are currently two strategies used for designing tumor-targeted probes. One is employing tumor-targeting agents and the other is tumormicroenvironment-activatable probes. Although these two strategies have been widely explored, there are few reports on the comparison of probe performance designed based on the two strategies. Herein, by targeting somatostatin receptors (SSTR) overexpressed in neuroendocrine tumors with octreotide (OCT), we have designed two probes, with probe P5 being tumor-microenvironment-activatable and P5cc(3) having fluorescence always on. A comparison of their selectivity toward tumor cells over SSTR-expressing normal cells demonstrated that these two probes showed a similar degree of tumor selectivity, whereas the activatable probe P5 showed enhanced tumor-to-normal imaging contrast due to its tumor-microenvironment-activatable fluorescence. Our results consolidate the rationality of either strategy for designing tumor-targeted imaging agents, and highlight the activatable strategy as a feasible way of enhancing tumor-to-normal imaging contrast.